European Thyroid Journal最新文献

Thyroid hormones are produced in the thyroid gland and metabolized in the peripheral tissues. The major pathway of thyroid hormone metabolism is the removal of an iodine atom from the phenolic or tyrosyl ring by deiodinating enzymes, the so-called deiodinases. Three distinct types of deiodinase have been identified, namely type 1 (D1), type 2 (D2) and type 3 (D3), which differ in main function and expression profile. Measuring the activities of D1, D2 and D3 is an indispensable tool in research on thyroid hormone metabolism. At present, only a limited number of research laboratories worldwide measure deiodinase activity using a variety of assays and protocols. Unlike diagnostic labs, research labs rarely participate in external quality control due to limited availability for most analytes or enzymes. However, implementing a quality assurance program for deiodinase assays is crucial to ensure consistent enzyme activity across laboratories. The present study provides the results of a method comparison between five established laboratories with experience in measuring deiodinase activity. The results showed that there are considerable differences in deiodinase activity levels determined by participating laboratories, which could be partially explained by differences in techniques and protocols. We therefore concluded that in most cases, absolute deiodinase activities can only be compared within the same laboratory. External quality control only adds value when all the laboratories use the same technique with their own optimized protocols. The use of internal controls is recommended to ensure that the correct enzymatic activity is being measured over time in the same laboratory.

Objective: Restoration of euthyroidism in patients with thyrotoxicosis prior to thyroidectomy is recommended to decrease perioperative morbidity and thyroid storm risk. This is challenging when conventional anti-thyroid medication is contraindicated or ineffective. Iopanoic acid (IOPA), an iodinated contrast medium formerly used as an oral cholecystographic agent, may facilitate treatment of thyrotoxicosis, but limited manufacture precludes its use in the UK. We investigated the effectiveness and safety of IOPA for optimizing thyroid status in treatment-resistant thyrotoxicosis prior to thyroidectomy at a referral centre.

Methods: With prior permission of our Drug and Therapeutics Committee, we sourced laboratory-grade (>98% pure) IOPA and administered this orally to control ongoing, severe thyrotoxicosis prior to thyroidectomy in 12 patients with inadequate response to standard therapies. Underlying aetiologies included Graves' disease, amiodarone-induced thyrotoxicosis, toxic multinodular goitre and resistance to thyroid hormone beta. Medical case notes were reviewed retrospectively to analyse clinical and biochemical outcomes.

Results: All patients exhibited a decline and normalization/near-normalization of free T3 (FT3) levels (mean 55% decrease, SEM 4.5%), with minimal changes in FT4 levels. Eleven patients proceeded to uneventful thyroidectomy, and IOPA was well tolerated with no directly attributable side effects.

Conclusion: IOPA is a safe and effective agent for controlling biochemical thyrotoxicosis in preparation for thyroidectomy, including disease refractory to conventional medication. Highly pure, laboratory-grade iopanoic acid that is approved for human use is now available in the UK; consideration should be given to more widespread use for emergency treatment of life-threatening hyperthyroidism.

Objective: Guideline-based lobectomy criteria were adopted in July 2017, and reflexive molecular testing (MT) was introduced for all Bethesda III/IV indeterminate thyroid nodules (ITNs) in July 2020. This study evaluates how reflexive MT of ITNs influenced lobectomy and completion thyroidectomy (CT) rates.

Methods: Patients with well-differentiated thyroid cancer who had undergone surgery were identified from a prospective database. Patients were categorized into three groups: i) Bethesda V/VI initial lobectomy, ii) Bethesda III/IV initial lobectomy without MT, iii) Bethesda III/IV lobectomy candidates with MT. The indications for and rates of lobectomy and CT, postoperative complications, and thyroid hormone replacement (THR) were assessed.

Results: From July 2017 to October 2023, 227 of 799 (28%) patients with thyroid cancer underwent initial lobectomy, with 91, 70, and 64 patients in each group, respectively. Included in group 3 were 16 ITNs that would have undergone diagnostic lobectomy; however, due to the presence of a malignant mutation, they underwent total thyroidectomy (TT). TT was the appropriate surgery for 15 of 16 patients based on either preoperative lobectomy exclusion criteria or final pathology. CT rates by group were 26, 43, and 27%, respectively (P < 0.05). Vascular invasion, tumor size >4 cm, and aggressive histology were the most common indications for CT. ThyroSPEC was independently associated with a lower likelihood of CT in multivariate analysis. Surgical complications were lower with lobectomy (2%) versus CT (7%), with 44% of lobectomy patients requiring THR.

Conclusion: Reflexive MT for ITNs decreased CT rates by increasing appropriate upfront TT. Lobectomy demonstrated lower rates of surgical complications and THR than two-stage thyroidectomy.

Background: Initial and dynamic risk stratification are crucial in managing pediatric differentiated thyroid carcinoma (DTC), aiming to guide treatment and long-term follow-up. While adult dynamic stratification is well established, pediatric data remain limited, and no formal recommendations exist for its use.

Objective: To evaluate the prognostic value of early dynamic risk stratification (EDRS) and postoperative stimulated thyroglobulin (sPOTg) in predicting long-term outcomes in pediatric DTC and to compare EDRS with initial ATA pediatric risk stratification (IRS).

Methods: We conducted a retrospective cohort study of 123 patients ≤18 years with DTC treated at a tertiary center. IRS and EDRS (1-3 years post-treatment) were compared to late dynamic response (LDRS, ≥10 years post-treatment). A total of 83 patients had complete long-term follow-up data. Associations were assessed using chi-square tests, logistic regression, Cohen's Kappa, and Cramér's V. ROC curve analysis evaluated the predictive value of sPOTg.

Results: Among 83 patients with ≥10 years of follow-up, EDRS showed a strong association with LDRS (Cramér's V = 0.829; p < 0.001), outperforming IRS (Cramér's V = 0.33; p = 0.0029). Concordance between EDRS and LDRS was substantial (Kappa = 0.79). Stimulated Postoperative Thyroglobulin (sPOTg) showed good discriminatory performance for disease persistence, with AUCs of 0.84 (95% CI: 0.70-0.95) at 1-3 years and 0.81 at ≥10 years.

Conclusion: Early dynamic response is a strong predictor of long-term outcomes and may surpass IRS in prognostic accuracy. sPOTg is a valuable biomarker for both early and late risk assessment. Prospective multicenter validation is warranted.

Objective: subacute thyroiditis (SAT) relapsing or refractory to standard of care oral prednisone (OP) therapy is rare, but affected patients experience significant discomfort due to prolonged and uncontrolled neck pain. Here we report the efficacy of high-dose intravenous methylprednisolone (IVMP) therapy in the treatment of such cases.

Methods: in this pilot study we included 14 patients diagnosed with SAT in the period 2014-2024, in a single center. Therapy consisted of 500 mg of IVMP, divided into two weekly infusions and titrated down based on clinical response. Thyroid function tests, thyroid ultrasound, inflammatory markers were assessed at baseline and throughout the follow-up up to 3 to 6 months after IVMP discontinuation.

Results: At baseline, 4 and 10 patients had thyrotoxicosis or were euthyroid, respectively. The median (IQR) duration of treatment was 26 days (21-38). At the end of the treatment, we observed a complete clinical, ultrasonographic and biochemical response in twelve patients (86%), whereas thirteen (93%) had immediate resolution of neck pain and thyrotoxicosis. Only one patient did not improve at the end of IVMP protocol, and she was the only one experiencing a delayed remission with persistent hypothyroidism. Mild grade 1 and 2 adverse events (hyperglycemia, arterial hypertension and neutrophilia) occurred in 8 out 14 patients.

Conclusion: IVMP therapy resulted in a rapid clinical and ultrasonographic improvement in most patients with relapsing subacute thyroiditis unresponsive to oral steroids. This response allowed for a shorter treatment duration, with good tolerability, minimal adverse events, and a low incidence of hypothyroidism during follow-up.

Objective: Electrochemiluminescence immunoassays (ECLIAs) are widely used for thyroid function testing but may be affected by rare assay interferences that can lead to misdiagnosis. We aimed to investigate the frequency and types of assay interferences in thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) measurements using the Roche ECLIA.

Methods: Between 2019 and 2023, 124,615 patients underwent thyroid function testing. Assay interference was suspected in 283 cases based on clinical-laboratory mismatch, thyroid hormone imbalance, or discrepancies between assay methods. Further validation assessed potential interferences.

Results: Of the total tests (TSH: 124,609; FT4: 116,012; FT3: 83,044), 71 interference cases were confirmed (TSH: 11 [0.009%], FT4: 6 [0.005%], FT3: 53 [0.064%]). FT3 interferences were mainly due to idiotype and anti-streptavidin antibodies. Macro-TSH was detected in six cases and often led to unnecessary levothyroxine treatment. Furthermore, most interferences were detected by recognizing hormonal imbalances rather than clinical symptoms.

Conclusion: FT3 tests are most prone to assay interference. Awareness of interference patterns and close collaboration between physicians and laboratory staff are essential to prevent diagnostic errors.

Background: Radiofrequency ablation (RFA) has emerged as a minimally invasive and effective alternative to surgery for benign thyroid nodules, providing a significant volume reduction and symptom relief. However, approximately one in five patients experiences regrowth requiring retreatment. This study aimed to identify robust predictive factors - spanning the pre-, peri-, and post-treatment periods - to guide patient selection and follow-up strategies.

Methods: In this retrospective cohort study, 293 patients underwent RFA for benign thyroid nodules at Pitié-Salpêtrière Hospital between 2018 and 2023. Retreatment, defined as a second RFA within five years, was the primary outcome. Twelve clinical and treatment variables were analyzed using univariate and multivariate logistic regression. Predictive performance was assessed with receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC) values.

Results: Sixty-one patients (20.8%) required retreatment. Among twelve parameters from three periods (pre-treatment, peri-treatment, and post-treatment), optimal multivariate models identified six significant ones. The pre-treatment growth rate (AUC = 0.808, OR = 1.505, 95% CI: 1.182-1.952, P < 0.001) and six-month viable volume (AUC = 0.886, OR = 1.252, 95% CI: 1.088-1.496, P < 0.001) showed the highest predictive accuracy. Optimal thresholds were 1.75 mm/year for pre-treatment growth rate and 4.45 mL for viable volume. Patients with viable volume ≤ 2.1 mL had a <5% risk of retreatment, compared to >70% when viable volume exceeded 18.05 mL. Four predictive abacuses were developed to facilitate clinical application.

Conclusion: Pre-treatment growth rate and six-month viable volume are strong, independent predictors of retreatment after RFA of benign thyroid nodules. Incorporating these parameters into clinical decision-making may enhance patient selection, tailor treatment intensity, and inform follow-up intervals, thereby reducing the risk of retreatment and improving cost-effectiveness.

Objective: To evaluate differences in clinical presentation, diagnostic and therapeutic modalities, and outcomes in two cohorts of patients with sporadic medullary thyroid carcinoma (MTC) from reference centres in Italy and the Netherlands. The two centres have different diagnostic approaches, including the use of routine calcitonin (CT) measurement.

Methods: A total of 165 patients (106 Italian and 59 Dutch) were retrospectively included. The cohorts were compared overall and according to diagnostic modality. Logistic regression and multivariable Cox proportional hazards models were used, as appropriate, to assess progression-free survival (PFS), disease-specific survival (DSS) and associated risk factors.

Results: The Dutch cohort presented with more advanced disease, as per higher TNM, AJCC staging, and significantly higher CT both preoperative and at last visit (P < 0.001). Dutch patients received more frequently second operations, radiotherapy, and systemic treatments. PFS and 10-year DSS were significantly lower in the Dutch cohort (P < 0.001 and P 0.01). Tumour size, nodal involvement, presence of distant metastases at diagnosis and progression during the follow-up were independent strong predictors of shorter PFS and DSS. Patients diagnosed via routine CT measurement showed a less aggressive presentation and more favourable outcome.

Conclusion: We compared for the first time two MTC cohorts from countries with different diagnostic and therapeutic approaches. Our data contribute to highlighting an association between routine CT measurement and MTC presentation and outcome, while suggesting that caution should be exercised when interpreting the differences among countries in MTC prevalence and clinical features.

Graphical abstract: A simplified figure displaying the main events leading to Hashimoto's thyroiditis and Grave's disease via Th1 and Th2 activation, and the potential sites of selenium (Se) action. (A) Activated by the dendritic cell, naïve helper T cells (CD4+ T cells) can mainly differentiate into two subsets, Th1 and Th2, which are crucial in orchestrating immune responses. Th1 cells produce tumor necrosis factor (TNF-a) along with interferon-γ (IFN-γ), exacerbating inflammation, in synergy with interleukin-6 (ΙL-6), leading to apoptosis (death of follicular cells). In parallel, oxidative stress induces activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reactive oxygen species (ROS) and the phosphorylation and degradation of NF-κB inhibitors, thereby allowing NF-κΒ to translocate to the nucleus. NF-κB acts in the nucleus as a master transcription factor in the nucleus, significantly increasing IL-6 production in various cell types. Se supplementation decreases IL-6 production, thereby mitigating the inflammatory process: it activates antioxidant enzymes and increases Treg cells, restoring the balance with Th17 cells. Th2, by producing interleukins, promotes B cell differentiation into plasma cells that produce massive amounts of IgG antibodies, which stimulate the TSH receptor on thyrocytes, promoting thyroid hyperplasia and hyperthyroidism. In mild thyroid eye disease (TED), Se abolishes the effects of oxidative stress in interorbital fibroblasts, reducing hyaluronic acid release, decreasing inflammation, and potentially lowering the production of glycosaminoglycans (GAGs). (B) Se enhances selenoprotein P (SELENOP) and glutathione peroxidase (GPX) activity; it is significantly involved in redox processes within the thyrocytes, scavenging H2O2, and its reactive by-products (e.g. hydroxyl radicals) through oxidation-reduction cycles. GPX neutralizes the hydrogen peroxide (H2O2) produced during thyroid hormone synthesis. This process is essential for maintaining a healthy balance (redox homeostasis) within the thyroid gland. The effects are inversely related to basal Se levels.

Background: Significant progress has been made in the management of thyroid eye disease (TED), based on the elucidation of important pathogenic mechanisms. This has led to novel therapeutics validated in randomized clinical trials. Autoreactive antigens that elicit specific orbital immune reactions have not yet been identified, although it has been shown that fibrocytes, circulating stem cells that differentiate into fibroblasts, are expressing the thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R) and may be stimulated in the orbit by a cascade of inflammatory reactions inducing adipogenesis.

Ted clinical assessment: Moderate-severe forms of TED are the target for immunosuppressive therapy. Improvement in the assessment of the active and progressive phase of disease is becoming compelling, as the outcome of a treatment depends on how early during the progressive phase the disease is treated. The clinical activity score may not always help define the right time for treating.

Therapy: In 2020, teprotumumab, an anti-IGF-1 receptor blocker, has been approved by FDA for the treatment of TED. Since then, other drugs were studied or are under investigation and will seek regulatory approval.

Microbiome and ted: A series of studies have investigated the role of microbiome in thyroid autoimmunity and TED more in detail, based on the observation that treatment with antibiotics may modify the disease phenotype in a murine model of TED.

Artificial intelligence: This approach is being studied for the assessment of TED, especially trying to standardize the use of orbital and facial images for improving the diagnosis of the disease in the early, progressive phase. In the future, these applications will allow the use of synthetic data, in addition to training on real patient images and data.